Why GILD release is bunk again

by Xinlitik

This GILD release is absurd. It’s an uncontrolled study of 5 vs 10 day treatment. 8% died in the 5 day and 11% in the 10 day. More were also discharged in the 5 day (60 vs 52%) and “clinically recovered” (65 vs 54%).

We dont have a control group so we have no idea if those numbers are good. They included “severe” patients who were NOT on a ventilator. No other high quality research specifically published those numbers to my knowledge, but the new york data showed 8% mortality among non ventilated hospitalized patients and 15% among ventilated (10% overall) (www.nejm.org/doi/full/10.1056/NEJMc2010419)

Not a whole lot of difference, is it? Best case, 8-11% mortality versus 15% but we know that 15% group is sicker, on ventilation already. Worst case, no effect at all with 8% mortality among non ventilated patients.

What is “Severe”? It’s not clear. According to their clinicaltrials.gov filing, the only thing related to disease severity I can find in the inclusion criteria is O2 sat <94%. They exclude people with liver or kidney dysfunction, or who are on ventilation. If that’s really the whole of it, “Severe” is a pretty weak designation. MOST hospitalized patients for COVID meet this criteria! The new york data doesn’t publish this number, but the series of the first 12 covid patients in america had 12/12 reaching <94% at some point (www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=5&ved=2ahUKEwi4pICA5o3pAhU8CTQIHfC1CCIQFjAEegQIBRAB&url=https%3A%2F%2Fwww.medrxiv.org%2Fcontent%2F10.1101%2F2020.03.09.20032896v1.full.pdf&usg=AOvVaw34JqTf84qOxyNsuTjMj7aa) So what does this mean? Their population is probably the same or very similar to the “non-ventilated” group at New York. Patients are generally not hospitalized with normal O2 sats – mild disease is sent home. Now, new york does report first 3 hour data for oxygen use (not saturation)- 48% within the FIRST 3 HOURS of admission were on oxygen (generally you won’t be on oxygen with a sat >94%). Gilead is light on the details with regards to when they are recruiting people – if it’s within hours of admission, sure, maybe only half of hospitalized patients meet their criteria. If not, then it’s well known that O2 sats drift downward as the disease progresses, so if they’re recruiting people along the way that will be MOST if not all hospitalized patients.

Further more, did you notice the trend between groups? The 5 day did marginally better without reaching significance (10 had 0.75 the odds of a good outcome versus 5). They did this study to find out if a shorter course worked. It’s always nice to see a “dose response curve” in trials like this. Basically, more drug is usually better… just not enough to merit increased cost or side effects. In this case, we have a trend toward less drug being better. That speaks to either statistical variance from a drug that doesn’t work, or a harmful drug. Now, 5% stopped due to side effects in the 5 day group vs 10% in the 10 day group, but there’s no logical reason to believe the increased stop rate occurred early on – each dose is the same, it’s just the length that’s modulated. So I would argue the difference in good outcomes is evidence against efficacy, not adverse effects.

I’m not buying these results until they publish the placebo controlled data. Fyi that china data was placebo controlled and showed jack.

 

 

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